Retroviruses are widespread in nature, sad infection with these agents is associated with neoplastic and other disease states in many vertebrates. Infection with nondefective retroviruses (i.e., encoding for at least the gag, poI, and env genes; but not for oncogenes) can induce neoplastic disease in a variety of animal species. For a review, see Pathogenesis of retrovirus-induced diseases, in Molecular Biology of Tumor Viruses: RNA tumor viruses, 2nd Ed., R. Weiss, N. Teich, H. Varmus and J. Coffin (eds), New York, Cold Spring Harbor Laboratory, 1984, pp. 785-998, hereby incorporated by reference. For example, lymphoid leukosis viruses (LLV), including the aetiological agent of avian leukosis, severely impact the poultry industry. Bovine leukemia virus (BLV), which is related to the human HTLV-I retrovirus discussed below, infects dairy herds, causing the disease known as enzootic bovine leukosis or lymphosarcoma in cattle. The retroviral agent (FeLV) of feline leukemia is also of significant veterinary concern. Other members of the retrovirus group, called lentiviruses, cause slowly progressive lethal diseases in sheep and goats, and possibly in humans.
Exogenous human retroviruses were recently discovered and have already been implicated as the aetiological agents of certain types of human leukemias and acquired immune deficiency syndrome (AIDS). HTLV-I (or ATLV) infects lymphocytes containing the OKT4 cell surface antigen and causes excessive proliferation of Impaired cells leading to a syndrome called adult T-cell leukemia (ATL). A second, related virus designated HTLV-II is associated with less aggressive T-cell leukemias. A third human retrovirus (HTLV-III, LAV, ARV, or HIV) also has tropism for OKT4.sup.+ helper but instead of excessive proliferation HTLV-IlI induces a cytopathic effect leading to depletion of the target cell population and resultant immunosuppression. The development of AIDS and pro-AIDS syndrome requires continuous infection and replication of HTLV-III in OKT4.sup.+ target cells. The genetic structures of these human retroviruses and the mechanisms by which they usurp host cell functions are considered novel among retroviruses; Wong-Staal and Gallo, Nature 317:395-403, 1985, hereby incorporated by reference.
One problem encountered during preclinical studies of the immunosuppressire viruses is that a dramatic loss of T-cell viability is noted within two to three weeks of infection with HTLV-III. As a result, special OKT4.sup.+ clones must be used that constitutively are at least partially resistant to the cell-killing effects of the retrovirus. A question then arises as to the applicability of negative controls (in terms of 100% cycopathic effect) in these systems. On the other hand, suitable positive controls (in terms of 100% inhibition of cytopathic effect) by which the efficacy of an experimental intervention can be monitored in vitro are also lacking.
Furthermore, no definitive therapy exists for the disease states associated with retroviral pathogens.